Effect of thrombin on the metabolism and function of murine macrophages

  • Macrophages are plastic and heterogeneous immune cells that adapt pro- or anti-inflammatory phenotypes upon exposure to different stimuli. Even though there has been evidence supporting a crosstalk between coagulation and innate immunity, the way in which protein components of the hemostasis pathway influence macrophages remains unclear. We investigated the effect of thrombin on macrophage polarization. On the basis of gene expression and cytokine secretion, our results suggest that polarization with thrombin induces an anti-inflammatory, M2-like phenotype. In functional studies, thrombin polarization promoted oxLDL phagocytosis by macrophages, and conditioned medium from the same cells increased endothelial cell proliferation. There were, however, clear differences between the classical M2a polarization and the effects of thrombin on gene expression. Finally, the deletion and inactivation of secreted modular Ca2+-binding protein 1 (SMOC1) attenuated phagocytosis by thrombin-stimulated macrophages, a phenomenon revered by the addition of recombinant SMOC1. Manipulation of SMOC1 levels also had a pronounced impact on the expression of TGF-β-signaling-related genes. Taken together, our results show that thrombin induces an anti-inflammatory macrophage phenotype with similarities as well as differences to the classical alternatively activated M2 polarization states, highlighting the importance of tissue levels of SMOC1 in modifying thrombin-induced macrophage polarization.

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Author:Ürün UkanORCiD, Fredy Andrés Delgado LagosGND, Sebastian KempfORCiD, Stefan GüntherORCiD, Mauro SiragusaORCiD, Beate FißlthalerORCiD, Ingrid FlemingORCiDGND
URN:urn:nbn:de:hebis:30:3-818451
DOI:https://doi.org/10.3390/cells11101718
ISSN:2073-4409
Parent Title (English):Cells
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2022/05/23
Date of first Publication:2022/05/23
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/01/29
Tag:SMOC1; macrophage polarization; thrombin
Volume:11
Issue:10, art. 1718
Article Number:1718
Page Number:17
First Page:1
Last Page:17
Note:
This work was supported by the Deutsche Forschungsgemeinschaft (GRK 2336 TP05 Project ID 321115009, SFB 834/3 A5 Project ID: 75732319, Cardio-Pulmonary Institute, EXC 2026, Project ID: 390649896).
Note:
Gefördert durch den Open-Access-Publikationsfonds der Goethe-Universität
Institutes:Medizin
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Medizin
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International